Valproic acid (valproate, Depakote, or Depakene) is an effective medication for absence seizures, generalized tonic-clonic seizures, and partial seizures, when administered alone or in conjunction with other antiepileptic agents.

The valproic acid that circulates in blood is 85% to 90% protein-bound under normal circumstances. In uremia or during concomitant therapy with other drugs that are highly protein-bound (such as phenytoin), valproic acid is displaced from protein, resulting in a higher free fraction of the drug circulating in blood.

Since neurologic activity and toxicity of valproic acid are directly related to the unbound fraction of drug, adjustment of dosage based on knowledge of the free valproic acid concentration may be useful in the following situations: concomitant use of highly protein-bound drugs (usually >80% bound), hypoalbuminemia, pregnancy, renal or hepatic failure, and in the elderly. In these situations, the total valproic acid concentration in the blood may underestimate the disproportionately higher free valproic acid fraction.

The generally acceptable range for total valproic acid used as a reference to guide its therapy is 50 to 125 mcg/mL. The corresponding range of free valproic acid concentration for clinical reference is 4 to 15 mcg/mL.

Low free valproic acid concentration relative to these ranges may suggest inadequate dosing, while a high free valproic acid concentration may be associated with toxic effects.

Because the concentration of valproic acid fluctuates considerably depending on the time from last dose, interpretation of the clinical significance of the valproic acid concentration must take into consideration the timing of the blood specimen. For this reason, 2 collections are sometimes made to assess the trough and peak concentrations.